I'm writing this sort of guide on how to address PSSD comprehensively (symptomatic relief only, but without letting homeostasis reverse the benefits or cause tolerance) and also how to beat it permanently (actual "cure", or reversal). The reason for starting this thread is that I get so many PMs and I'm extremely busy in life, so I reply super-late, which I feel is bad since I want to help everyone get on the right track ASAP.

A little about me: many people have voiced concern on how I get my drugs. I'm a certified pharmacist, and I've provided proof to admins, and can provide further proof if need be. I didn't want to reveal my occupation because of fears that my posts would gain traction based on this alone, and being taken at face value without people double-checking the neurochemical and pharmacological information I provide. After all, I can merely offer educated guesses.

I've managed to achieve a 90% symptomatic relief (NOT a cure/reversal), but I will not post about my regimen until 1-2 months from now to make sure that the benefits are sustainable and there's no sign of tolerance. The worst thing a person can do to this community is over-hyping a treatment plan that would ultimately fail and giving false hope. I will avoid that.

This thread will be work-in-progress, and I will keep updating the OP as I have free time. I firmly believe that each person's PSSD is different and different pathways are affected, with some dysregulated pathways in-common, and a "general" guideline is needed to make you think how to address your own PSSD.

These are the main point that I will address here:1. Fix gut dysbiosis and micro-organism overgrowth. Many people experience gut problems after PSSD. H2S and ammonia producing bacteria can cause neurological symptoms similar or more severe than PSSD. Candida should also be addressed.

2. Addressing the hormonal issues, at least to the best of our abilities.

3. Finding symptomatic relief long-term (without being counteracted by homeostasis). In this part, we shouldn't use directly acting agonists that would cause downregulation/tolerance, or hormonal replacement that would cause shutdown, without utilizing agents that upregulate said receptors, or depend on rebound phenomenon, or just use a partial agonist instead, etc.

Important rule: Avoid polypharmacy as much as possible, and be minimalistic with dosing.

I will go in-depth on each point, once I have any free time. Stay tuned.

Last edited by Mesolimbo on Thu Mar 14, 2019 4:01 am, edited 2 times in total.

Like a robot attempting to fix its own faulty programming1. Fix the gut/hormones.2. Find a symptomatic relief not counteracted by homeostasis.3. Work on permanent solution through TrkB, BDNF, and NGF.4. Decrease microglia activation.

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Step 1: Gut microbiome dysbiosisMany people report experiencing significant gut problems after getting PSSD. Many antidepressants are reported to have antimicrobial effect [1] and have a synergistic effect with antibiotics [2]. They seem to alter the gut microbiome, but the data is inconclusive on what changes they induce.

Certain bacteria can turn sulfur into the rotten egg smelly hydrogen sulfide gas (H2S), which is toxic to the nervous system and the mitochondria. If you start experiencing sulfur compounds/food intolerance, as such garlic and onion making you feel a ton worse, then you may have this dysbiosis. Rotten egg smelling flatulence is another tell-tale sign.

Another harmful bacterial overgrowth is the urease-producing bacteria which increase systemic ammonia. The liver is efficient in its ability to clear out the excess ammonia, but if there's liver impairment, expect severe neurological symptoms, which can also be mistaken for PSSD.

To make things worse, microbiome dysbiosis is associated with autoimmune conditions and neurodegeneration. Those bacteria release endotoxins leading to the activation of immune response and systemic inflammation. Changes in intestinal tight junctional proteins and increased gut permeability make sure that these toxin reach the systemic circulation. [3]

The body starts the synthesis of the proinflammatory cytokines TNF-α, IL-1β and IL-6. Activation of NF-κB and subsequent stimulation of toll-like receptors (TLR2 and 4) cause the brain microglia to switch on to their "active/reactive" state. [4][5]

This is bad because the microglia switches on to "Kill and eat" state, producing neuroinflammatory cytokines and stimulating apoptosis. They can remain in this state semi-permanently under certain conditions [6]. This would cause neuroinflammation and degeneration due to dysregulated apoptotic mechanisms (c-Jun N-terminal kinase (JNK) pathway).

What to do about gut microbiome dysbiosis?Find a knowledgeable professional who would carry out SIBO tests for you, such as the hydrogen breath test (HBT). Make sure that this physician knows that H2S producing bacteria cannot be detected by oral lactulose test.

Work with your physician to change your diet, repair your gut with glutamine, prebiotics, probiotics, and sometimes a course of Rifaximin is also needed. The treatment plan depends on which dysbiosis you have and how bad it is.

Remember: Your PSSD symptoms may actually be symptoms of neurotoxicity caused by gut dysbiosis. Many of H2S or ammonia toxicity symptoms may be mistaken for PSSD symptoms due how similar they are [17] . Before attempting to target PSSD, make sure that you no longer have any gut-brain axis problem.

Last edited by Mesolimbo on Fri Mar 15, 2019 4:08 am, edited 2 times in total.

Like a robot attempting to fix its own faulty programming1. Fix the gut/hormones.2. Find a symptomatic relief not counteracted by homeostasis.3. Work on permanent solution through TrkB, BDNF, and NGF.4. Decrease microglia activation.

I'll be following this thread as well! I had been experiencing more and more good days and "windows," but I think the use of so many drugs (polypharmacy) in an attempt to further, or finalize, my progress has actually reversed it. Fuck.

I've added the first step "Step 1: Gut microbiome dysbiosis". This is a very important step to address before even thinking about managing PSSD.

Like a robot attempting to fix its own faulty programming1. Fix the gut/hormones.2. Find a symptomatic relief not counteracted by homeostasis.3. Work on permanent solution through TrkB, BDNF, and NGF.4. Decrease microglia activation.

Everything written here MAKES A LOT OF SENSE! At least in my case! I have developed extreme intolerance to garlicky food since pssd, makes me bloated, tired,sick and makes my pssd symptoms a lot worse, even increases my anhedonia!

The body starts the synthesis of the proinflammatory cytokines TNF-α, IL-1β and IL-6. Activation of NF-κB and subsequent stimulation of toll-like receptors (TLR2 and 4) cause the brain microglia to switch on to their "active/reactive" state. [4] [5]

This is bad because the microglia switches on to "Kill and eat" state, producing neuroinflammatory cytokines and stimulating apoptosis. They can remain in this state semi-permanently under certain conditions [6]. This would cause neuroinflammation and degeneration due to dysregulated apoptotic mechanisms (c-Jun N-terminal kinase (JNK) pathway).

Neuroinflammation is closely associated with the pathogenesis of Parkinson’s disease (PD) and other neurological disorders. The hallmark of neuroinflammation is microglial activation. Increasing evidence suggests that inhibition of microglia-mediated neuroinflammation might represent a promising therapeutic potential for PD and related disorders. Fluoxetine, a selective serotonin reuptake inhibitor, is commonly used for the treatment of major depression due to its tolerability and safety profiles. Recent studies have shown that fluoxetine affords robust neuroprotection in a series of neurological disease models. However, the mechanism underlying fluoxetine-mediated neuroprotection remains unclear. Here, by using rat primary midbrain neuron-glia cultures, we report that both R and S isomers of fluoxetine attenuated chronic neurodegeneration induced by a commonly used inflammogen lipopolysaccharide (LPS). Reconstituted cell culture studies further revealed that microglia were required for fluoxetine-mediated neuroprotection. Fluoxetine significantly inhibited LPS-induced activation of microglia and subsequent release of multiple pro-inflammatory and cytotoxic factors including tumor necrosis factor-α, interleukin-1β, nitric oxide, and reactive oxygen species. Furthermore, inhibition of microglial NF-κB signaling pathway participated in fluoxetine-mediated neuroprotection. Collectively, fluoxetine exerted neuroprotection against microglia-mediated neurotoxicity. Thus, fluoxetine not only can relieve depression, a common nonmotor symptom of PD, but might also hold a potential to retard inflammation-mediated chronic neurodegenerative process of this disease.

Sorry that I'm not around. I've been extremely busy at work and with moving out. I'll be back to the forum once I'm over this stressful period.

Like a robot attempting to fix its own faulty programming1. Fix the gut/hormones.2. Find a symptomatic relief not counteracted by homeostasis.3. Work on permanent solution through TrkB, BDNF, and NGF.4. Decrease microglia activation.